Nedberg Nora Hersoug, Nystad Mona, Ahlen Maria Therese, Bertelsen Eirin Listau, Guz Katarzyna, Uhrynowska Małgorzata, Dębska Marzena, Gierszon Agnieszka, Orzińska Agnieszka, Husebekk Anne, Brojer Ewa, Staff Anne Cathrine, Tiller Heidi
Immunology Research Group, Department of Medical Biology, Faculty of Health Sciences, UiT the Arctic University of Norway, Tromsø, Norway; Women's Health and Perinatology Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT the Arctic University of Norway, Tromsø, Norway.
Women's Health and Perinatology Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT the Arctic University of Norway, Tromsø, Norway; Department of Obstetrics and Gynecology, University Hospital of North Norway, Tromsø, Norway.
Placenta. 2024 Dec;158:185-191. doi: 10.1016/j.placenta.2024.10.014. Epub 2024 Oct 24.
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from parental incompatibility in human platelet antigens (HPA) and subsequent maternal sensitization. The HPA-1a epitope is also expressed on placental tissue. Chronic placental inflammation and lower birth weight is observed more often in HPA-1a alloimmunized pregnancies, suggesting a placental component in the pathophysiology of FNAIT. Today, prediction of FNAIT severity is limited. The aim of the study was to investigate whether dysregulated maternal angiogenic proteins are associated with neonatal outcome in HPA-1a alloimmunized pregnancies.
Eighty-seven HPA-1a negative pregnant women were identified from a large prospective screening study in Poland (PREVFNAIT) including 43 HPA-1a immunized and 44 non-immunized controls. Placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in maternal plasma from 2nd and 3rd trimester by enzyme-linked immunosorbent assay and levels/ratios were compared between study groups, using uni- and multivariable analyses. Main outcome measures were either classic FNAIT-related (severe thrombocytopenia, petechia, intracranial hemorrhage), placenta-related (small for gestational age) or a composite variable combining them all.
There were no significant differences in plasma concentrations of sFlt-1, PlGF, sEng nor sFlt-1/PlGF ratio when comparing immunized and non-immunized pregnancies. Among HPA-1a alloimmunized pregnancies, increasing levels of the sFlt-1 protein in 3rd trimester were significantly associated with lower neonatal platelet count (multivariable linear regression, p = 0.024). Increased sFlt-1 and sFlt-1/PlGF ratio in 3rd trimester were significantly associated with higher odds of a composite adverse neonatal outcome in alloimmunized pregnancies (multivariable logistic regression, p = 0.029 and p = 0.019, respectively).
An anti-angiogenic profile in HPA-1a alloimmunized mothers is associated with a composite adverse neonatal outcome. This suggests that sFlt-1 and the sFlt-1/PlGF ratio may assist in predelivery risk stratification and clinical management decisions for FNAIT.
胎儿及新生儿同种免疫性血小板减少症（FNAIT）是由人类血小板抗原（HPA）的亲代不相容性以及随后的母体致敏引起的。HPA-1a表位也在胎盘组织中表达。在HPA-1a同种免疫的妊娠中，慢性胎盘炎症和较低出生体重更为常见，这表明胎盘在FNAIT的病理生理学中起作用。如今，FNAIT严重程度的预测有限。本研究的目的是调查母体血管生成蛋白失调是否与HPA-1a同种免疫妊娠的新生儿结局相关。
从波兰一项大型前瞻性筛查研究（PREVFNAIT）中确定了87名HPA-1a阴性孕妇，其中包括43名HPA-1a免疫孕妇和44名非免疫对照。在孕中期和孕晚期通过酶联免疫吸附测定法测量母体血浆中的胎盘生长因子（PlGF）、可溶性fms样酪氨酸激酶-1（sFlt-1）和可溶性内皮糖蛋白（sEng），并使用单变量和多变量分析比较研究组之间的水平/比率。主要结局指标为经典的FNAIT相关指标（严重血小板减少、瘀点、颅内出血）、胎盘相关指标（小于胎龄）或综合这些指标的复合变量。
比较免疫妊娠和非免疫妊娠时，sFlt-1、PlGF、sEng的血浆浓度以及sFlt-1/PlGF比率均无显著差异。在HPA-lla同种免疫妊娠中，孕晚期sFlt-1蛋白水平升高与新生儿血小板计数降低显著相关（多变量线性回归，p = 0.024）。孕晚期sFlt-1和sFlt-1/PlGF比率升高与同种免疫妊娠中复合不良新生儿结局的较高几率显著相关（多变量逻辑回归，分别为p = 0.029和p = 0.019）。
HPA-1a同种免疫母亲的抗血管生成特征与复合不良新生儿结局相关。这表明sFlt-1和sFlt-1/PlGF比率可能有助于FNAIT的产前风险分层和临床管理决策。
